Principal Supervisor: Dr Matthias Soller, School of Biosciences
Co-supervisor: Dr Pawel Grzechnik, School of Biosciences
Leicester collaborator: Cyril Dominguez, Department of Molecular and Cell Biology, University of Leicester
PhD project title: mRNA epigenetics: Charaterization of novel layer of gene regulation for essential brain functions
University of Registration: University of Birmingham
For over 40 years we know about modified nucleotides in mRNA, but the functions for these essential modifications are largely elusive. Recent characterization of the FTO (fat mass and obesity associated) gene as a demethylase indicates key roles for mRNA methylation in neuronal control of body weight1. FTO is highly expressed in the brain and has also been associated with other neurological disorders such as depression, epilepsy and Alzheimers disease.
We use a Drosophila genetic model system to investigate the biological function of these modifications2. Our aim is to identify which mRNAs are modified and where in these mRNAs modifications are localised. Furthermore, we aim to characterize the molecular machinery that places these modifications and the signalling pathways that regulate the dynamics of them. Last, we like to know the biological functions for these modifications.
- Dezi, V., Ivanov, C., Haussmann, I. U. and Soller, M. (2016) mRNA modifications and their role in development and disease. Biochem. Soc. Trans. 44: 1385-93.
- Haussmann, I.U., Bodi, Z., Sanchez-Moran, E., Mongan, N., Archer, N., Fray, R., and Soller, M. (2016) m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature, doi:10.1038/nature20577.
BBSRC Strategic Research Priority: Molecules, Cells and Systems
Techniques that will be undertaken during the project:
This project will incorporate a wide range of molecular and cell biology techniques, which will be applied by using the genetic model organism Drosophila and various cell culture models. The project will make use of state-of-the-art cellular imaging to study mRNA methylation in cells. Further, we will employ structural characterization of mRNA methylation components, apply statistical analysis of data and use molecular modelling of structural information to make predictions how mRNA methylation takes place in cells.
Contact: Dr Matthias Soller, School of Biosciences